Cannabis Flashcards
Absolute Contraindications to Medical Cannabis
● psychosis in patient history or that of their first degree relative
● mania (no THC-CBD only products may be an option)
●active substance abuse disorder
●pregnancy
● breastfeeding
Relative Contraindications to Medical Cannabis
● Cannabis use disorder
● Mania
● COPD - vape worsen chronic lung disease
● Cirrhosis esp. Hepatitis-C related: worsening fibrosis
● Patient on a cancer immunotherapy agent ? effects
Relative Contraindications to Medical Cannabis 2
● Cardiovascular disease
● Post Myocardial infarction (2 months post MI)
● Atrial Fibrillation
● Cardiac arrhythmia
● Patient on anticoagulant drug
Relevant Interactions
● Warfarin & Oral Anticoagulants - CBD possibly able to increase drug levels
One case study of CBD increasing INR
Possible increase in clobazam levels from CBD (especially when > 100mg)
CBD is an inhibitor of CYP3A4 (St.Johns Wort & Grapefruit also) which metabolizes quarter of all drugs
CBD is a inhibitor of CYP2D6 (metabolizes many psychiatric medicines:
SSRIs, tricyclic antidepressants, antipsychotics)
THC is a CYP1A2 inducer - decrease serum
concentrations of clozapine, duloxetine, naproxen, cyclobenzaprine,
olanzapine, haloperidol, and chlorpromazine
Cannabis Pearls
Routinely ask about cannabis use in primary care (just like tobacco and alcohol), & monitor for cannabis use disorder.
After failure of ≥3 other drugs, a trial of prescription cannabinoids (rather than cannabis) may be reasonable for treating neuropathic pain.
2 Approach cannabinoids with similar caution as opioids – see box below. Start cannabinoids at a low dose, and gradually titrate. A few clinical trials suggest some efficacy even at very low doses.
Adverse effects are common; monitor; stop or taper if not tolerated. Inhaled cannabis is not a preferred route of administration due to difficulty dosing, risk of respiratory damage, and multi-component composition.
The potential harms of cannabinoids are often underappreciated by patients. Informed consent and patient education are advisable.
Do Cannabinoids Work (Medicinally)?
- Chronic neuropathic pain NNT=11 for ≥30% reduction over ~4 wks.
- Chemotherapy-induced nausea & vomiting NNT=3 for control of nausea/vomiting over ~1 day.
- Spasticity of multiple sclerosis or spinal cord injury NNT=10 for ≥30% spasticity over ~6 wks.
- Seizures in Lennox-Gastaut & Dravet syndrome with CBDNNT=4-7 for ≥50% reduction in seizure frequency over ~14 wks.
- Cachexia in HIV/AIDS, cancer, palliative care: weak evidence.
Are Cannabinoids Safe?
Approximately 8-9 patients out of 10 will develop an adverse effect to cannabinoid therapy
Approximately 1 patient in 10 will stop therapy because of an adverse effect:
- feeling “high” NNH=4;
- sedation NNH=5;
- speech disorders NNH=5;
- dizziness NNH=5; and
- ataxia/muscle twitching NNH=6.2
Additional concerns include driving impairment, addiction risk, euphoria, and psychosis.
Cannabinoids for pain, or Opioids …
Trial evidence comparing cannabinoids and opioids is limited. But they do have some similarities and differences to consider:
Efficacy: For both drug classes, RCT evidence is of low quality and short duration, and tends to show only a modest reduction in pain. Longer trials tend to show less benefit. However, despite the relative lack of quality evidence, patients often have strong beliefs about the value of each drug class.
Adverse effects: Nausea, sedation, and euphoria are adverse effects of both drug classes. Opioids can cause constipation; cannabinoids can cause psychiatric disturbances (e.g. anxiety, agitation, amotivation, psychosis).
Adverse effects appear dose-related (dose = AE). Both drug classes may be used by patients as an “escape”.
Addiction risk: With prescription opioids, estimated to be 5.5%. With non-medical cannabis, estimated to be 9%. (The risk with medical cannabinoids is unstudied.)
Fatal overdose risk: With prescription opioids, 0.23% with >100mg morphine per day (↑risk with ↑dose).25 With cannabis, fatal overdose risk appears to be negligible.
For both drug classes, the concept of a trial with an exit strategy is important. Not all patients will respond to these medications.
Nabiximols SATIVEX extracted THC/CBD
2.7mg THC & 2.5mg CBD per spray
(peppermint flavour; poor taste)
(contains alcohol)
Refrigerate prior to dispensing
Preferred over cannabis.CFP’18
advanced cancer pain (adjunctive)
multiple sclerosis neuropathic pain or spasticity (adjunctive)
Spasticity may require lower doses than pain (e.g. 4-5 sprays vs >8 sprays per day).
Detected in SK urine drug screen
Spray under the tongue or into side cheek (may alternate sides).
Shake vial gently. Device requires priming (3 sprays).
Initial: 1 spray sublingually HS
Usual: 1 spray sublingually q4h
Usual max: 12 sprays per day
3 vial pack = $700
Cannabidiol EPIDIOLEX extracted CBD
100mg/mL solution FDA’18
(contains alcohol, sesame oil; strawberry flavour)
Treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients ≥2 years of age
Not detected in SK urine drug screen
Seizures (Lennox-Gastaut or Dravet): ≥2yrs: 2.5-10mg/kg/dose po BID usually give before a meal
Food fat/caloric increases absorption.
Dronabinol MARINOL synthetic THC
USA only
2.5, 5mg, 10 cap (in sesame oil)
5mg/mL solution SYNDROS
(contains alcohol)
Severe nausea/vomiting from cancer chemotherapy
AIDS-related anorexia Initial: 2.5mg po HS
Usual:
2.5-5mg po TID-QID for chemo nausea/vomiting (~5mg/m2)
2.5mg po BID ac lunch and supper for anorexia AIDS 3
Max: 20mg/day
Oral Cannabis Oils THC/CBD in various ratios
Dried Cannabis
THC/CBD in various ratios, often to smoke/vape, e.g.:
12.5% THC
4% THC / 10% CBD
1% THC / 13% CBD
Medically authorized in Canada to any patient for any indication (i.e., “off-label use”).
THC detected in urine drug screen up to 4 weeks after last dose (esp. chronic/heavy users).
Oral vs inhaled: Oral has lower bioavailability (~10% vs ~25%), slower onset (30-60min vs 5-10min),4 longer duration (4-8 hrs vs 2-4 hrs),1 & does not have respiratory risk.
Smoked vs vaped: smoking speculated to have more respiratory risk (but data limited), but vaping has risk too (2,602 reports of vaping lung injury in US).
Vaping ~2x more potent (smoking destroys some drug via combustion).
500mg cannabis x 10% THC x 50% loss to combustion ≈ 25mg THC
Cannabis Dosing
Initial: 2-3mg of CBD +/- THC po HS (e.g. 0.1mL of 20mg/mL CBD) Usual: Uncertain due to lack of randomized trials. Titrate slowly. (Consider: dronabinol & nabiximols labelling suggest max doses of 25-30mg THC per day.)
Food increases absorption.
Consider 1st dose at 7 p.m. to leave time for assessing effect. Consider weekend trial start (or when impairment less disastrous).
Guidelines recommend avoiding smoked cannabis.2,7
Initial: 1-2 puffs inhaled HS (1 puff of joint ≈ 1‐10mg THC.
Variation is due to inhalation depth, puff size, THC potency, smoked vs vaped, joint size, etc.)
Usual: Uncertain due to poor quality evidence. Titrate slowly. Based on market data for 2017 in Canada, medical cannabis patients titrated themselves to an average dose of 750mg dried cannabis per day. Canada, the average retail price was $10/g and the average street price was $6/g: $12-24 for 1-2 puff HS, $180 for 750mg/day, $720 for 3g/day
Some notes on adverse effects: percentages below are often “worst case scenarios” from systematic reviews, yet due to trial-design issues could also be underestimates. adverse effects appear dose-related (dose = AE) it is difficult to compare AE rates between agents, due to few head-to-head trials.
THC appears to be the main component responsible for causing a “high” (low quality evidence).
CBD possibly safer than THC, but some of its psychotropic effects are underappreciated (e.g. vs placebo in predominately pediatric trials: aggression/anger 3-5% vs <1%; irritability/agitation 5-9% vs 2%; somnolence 25% vs 8%).
Drowsiness or sedation up to 50% across cannabinoids, dizziness up to 32% across cannabinoids, psychiatric disturbances up to 17% across cannabinoids and up to 27% with inhaled cannabis.
COMPASS including depression, anxiety, panic, paranoia, hallucination. In Colorado, accounts for ~25% of cannabis related hospital visits.Monte’19 euphoria up to 15%, and feeling “high” up to 35% across cannabinoids.2 acute psychosis or dissociation up to 5% across cannabinoids.2 1st episode psychosis daily cannabis ↑3x & THC ≥10% ↑5x vs never users.
Schizophrenia unmasking: cannabis may hasten first psychotic episode by 2-6 yrs.8 speech disorders up to 32%, and ataxia up to 30% across cannabinoids. Impaired memory up to 11% across cannabinoids. Irritability or agitation up to 9%, and anger or aggression up to 5% with CBD.
Appetite changes: decreased appetite in up to 22% of patients on CBD but conversely increased appetite in up to 38% of patients on dronabinol
GI issues: dry mouth; diarrhea up to 20%, vomiting up to 15% with CBD.
Conversely nausea in up to 20% of pts with dronabinol.
SATIVEX: mouth irritation. In Colorado, accounts for ~30% of cannabis related hospital visits.
Cannabis hyperemesis syndrome: severe abdominal pain/vomiting; requires drug discontinuation; relieved by hot shower; applying capsaicin to abdomen useful.32 pneumonia up to 8% with oral CBD.31
LFTs up to 16% of pts on CBD;31 ?related to concomitant valproate/clobazam. driving impairment: risk of fatal car crash approximately doubles with THC.28,55 withdrawal with abrupt discontinuation (see withdrawal symptoms on next page) red eyes reported with non-medical use of oral and smoked THC. rare or uncertain: ?sexual problems, ?cancer testicular, ?BMD, ?pancreatitis
Contraindications
Caution
CI: pregnancy ↓birth Wt, ?↑preterm/stillbirth, ?negative neurodevelopment; breastfeeding; < 21-25yrs (CBD exception: tx-resistant seizures); psychosis/schizophrenia hx.
Caution: in elderly, substance abuse history, driving (sometimes a contraindication) <4hrs after inhalation / <6hrs after ingestion / <8 hrs after euphoria (driving impairment studies have focused on THC component); hx of seizures, psychiatric disorders (eg bipolar, anxiety), CVD, or respiratory disease.
